PROJECT SUMMARY/ABSTRACT Schistosomiasis is a chronically debilitating disease caused by parasitic schistosome worms infecting over 200 million people resulting in over 280,000 deaths annually due to complications from the disease. Schistosome larvae, cercariae, exit freshwater snail species and burrow into human skin through the use of proteases that degrade skin proteins. Afterwards they transform into schistosomula, enter the bloodstream, eventually arriving at the mesenteric veins where the adult worms eat red blood cells, pair, and lay hundreds of eggs daily. Although schistosomes have been studied more than 150 years, we know little of the molecular regulators that modulate the development of cercariae to schistosomula and the adaptation from free-swimming parasites to blood-dwelling worms. This proposal will identify the unidentified and uncharacterized initial regulators of development found static in cercariae and develop a comprehensive timeline of the developmental progression from cercariae to schistosomula. These data will provide clues to begin to further explore the mechanisms for the developmentally regulated translational control of the schistosome life cycle that may be conserved in other organisms.